1999 Fiscal Year Final Research Report Summary
Significance of immunological tolerance on development and progress of hepatocellular carcinoma and proposal for a novel therapeutic approach Experimental study on murine liver tumor using MH-134 hepatoma cells mouse liver transplantation model
| Project/Area Number |
10671226
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Fujita Health University |
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Principal Investigator |
UYAMA Ichiro Fujita Health Univ., Dept. of Surgery, instructor, 医学部(消化器外科), 講師 (60193950)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Miwa Fujita Health Univ., Dept. of Surgery, researcher, 医学部(消化器外科), 研究員
SUGIOKA Atsushi Fujita Health Univ., Dept. of Surgery, Assistant Professor, 医学部(消化器外科), 助教授 (20171150)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Mose liver transplantion / immunological tolerance / hepatocellular carcinoma / anti IL-4 monoclonal antibody / MH134 |
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| Research Abstract |
It was hypothesized that immunological tolerance plays an essential role in development and progression of hepatocellular carcinoma(HCC) to which the carrier state of hepatitis viruses generally predisposed. Therefore, the experiments using orthotopic mouse live transplantation model (OMLT: C3H/He->DBA/2) are expected to the optimal in evaluation the significance of immunological tolerance because immunological tolerance is achieved as a rule. First, the number of HCC nodules developed in the recipient's liver was estimated after the injection of MH-134 heptoma cells via portal vein at various timing after liver transplantation, i.e. Day14, Day28, Day42, and Day100. The result showed that the degree of immunological tolerance in recipients have a significant influence on the number of HCC nodules. Second, the effect of anti IL_4 monoclonal antibody(11B11) was evaluated. IL-4 is regarded as an essential mediator of immunological tolerance. Our previous data showed that neutralization of IL-4 with 11B11 on Day28 or Day42 prevented induction of tolerance but not on Day100 when immunological tolerance is established. In this study, recipients were divided into two groups, i e. the control group : recipients were simultaneously injected 4mg of Rat IgG intraperitoneally and MH-134 hepatoma cells (1×10ィイD18ィエD1cells) via portal vein on Day14, Day28, Day42, and Day100, and the experimental group : recipients were injected 4mg of 11B11 and MH-134 hepatoma cells similarly. The experimental group developed significantly larger number of HCC nodules when 11B11 and MH-134 heptoma cells were injected on Day28 and Day42 but not on Day100. These data also suggested that immunological tolerance or IL-4 is essential for development and progression of HCC. In conclusion, host immunological tolerance could be a new target in the treatment of HCC.
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